Signal peptide and helical bundle domains of virulent canine distemper virus fusion protein restrict fusogenicity.

Détails

ID Serval
serval:BIB_D3707777829B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Signal peptide and helical bundle domains of virulent canine distemper virus fusion protein restrict fusogenicity.
Périodique
Journal of Virology
Auteur(s)
Plattet P., Cherpillod P., Wiener D., Zipperle L., Vandevelde M., Wittek R., Zurbriggen A.
ISSN
0022-538X[print], 0022-538X[linking]
Statut éditorial
Publié
Date de publication
10/2007
Volume
81
Numéro
20
Pages
11413-11425
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Persistence in canine distemper virus (CDV) infection is correlated with very limited cell-cell fusion and lack of cytolysis induced by the neurovirulent A75/17-CDV compared to that of the cytolytic Onderstepoort vaccine strain. We have previously shown that this difference was at least in part due to the amino acid sequence of the fusion (F) protein (P. Plattet, J. P. Rivals, B. Zuber, J. M. Brunner, A. Zurbriggen, and R. Wittek, Virology 337:312-326, 2005). Here, we investigated the molecular mechanisms of the neurovirulent CDV F protein underlying limited membrane fusion activity. By exchanging the signal peptide between both F CDV strains or replacing it with an exogenous signal peptide, we demonstrated that this domain controlled intracellular and consequently cell surface protein expression, thus indirectly modulating fusogenicity. In addition, by serially passaging a poorly fusogenic virus and selecting a syncytium-forming variant, we identified the mutation L372W as being responsible for this change of phenotype. Intriguingly, residue L372 potentially is located in the helical bundle domain of the F(1) subunit. We showed that this mutation drastically increased fusion activity of F proteins of both CDV strains in a signal peptide-independent manner. Due to its unique structure even among morbilliviruses, our findings with respect to the signal peptide are likely to be specifically relevant to CDV, whereas the results related to the helical bundle add new insights to our growing understanding of this class of F proteins. We conclude that different mechanisms involving multiple domains of the neurovirulent A75/17-CDV F protein act in concert to limit fusion activity, preventing lysis of infected cells, which ultimately may favor viral persistence.
Mots-clé
Animals, Distemper Virus, Canine/chemistry, Distemper Virus, Canine/pathogenicity, Dogs, Mutation, Missense, Protein Sorting Signals, Protein Structure, Tertiary, Viral Fusion Proteins/chemistry, Viral Fusion Proteins/genetics, Virulence
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 10:43
Dernière modification de la notice
20/08/2019 15:53
Données d'usage